ProjectThe design and development of efficient biocatalytic cascades and biosynthetic pathways for the sustainable production of amines

Researcher (PI)Francesco Mutti

Host Institution (HI)UNIVERSITEIT VAN AMSTERDAM

Call DetailsStarting Grant (StG), LS9, ERC-2014-STG

SummaryThe objective of this project is to design and develop biocatalytic cascades, using purified enzymes in vitro, as well as biosynthetic pathways in whole cell microbial organisms. These biocatalytic cascades and biosynthetic pathways will be developed for the synthesis of chiral and achiral amines that are of particular interest for the chemical industry. The amine functionality will be introduced using amine dehydrogenases (AmDHs) as biocatalysts in the pivotal core enzymatic step. AmDHs are a new class of enzymes that have recently been obtained by protein engineering of wild-type amino acid dehydrogenases. However, only two AmDHs have been generated so far and, moreover, they show a limited substrate scope. Therefore protein engineering will be undertaken in order to expand the substrate scope of the already existing AmDHs. In addition, novel AmDHs will be generated starting from different wild-type amino acid dehydrogenases as scaffolds, whose amino acid and DNA sequences are available in databases, literature, libraries, etc. In particular, protein engineering will be focused on the specific chemical targets that are the objectives of the designed biocatalytic cascades and in addition, screening for more diverse substrates will also be carried out. Finally, the AmDHs will be used in combination with other enzymes such as alcohol dehydrogenases, oxidases, alkane monooxygenases, etc., to deliver variously functionalised amines and derivatives as final products with elevated yields, perfect chemo- regio- and stereoselectivity, enhanced atom efficiency and minimum environmental impact. Such an approach will be realised through the design of new pathways that will convert inexpensive starting materials from renewable resources, encompassing the internal recycling of redox equivalents, the use of inorganic ammonia as nitrogen source and, if necessary, only molecular oxygen as the innocuous additional oxidant. Water will be the sole by-product.

The objective of this project is to design and develop biocatalytic cascades, using purified enzymes in vitro, as well as biosynthetic pathways in whole cell microbial organisms. These biocatalytic cascades and biosynthetic pathways will be developed for the synthesis of chiral and achiral amines that are of particular interest for the chemical industry. The amine functionality will be introduced using amine dehydrogenases (AmDHs) as biocatalysts in the pivotal core enzymatic step. AmDHs are a new class of enzymes that have recently been obtained by protein engineering of wild-type amino acid dehydrogenases. However, only two AmDHs have been generated so far and, moreover, they show a limited substrate scope. Therefore protein engineering will be undertaken in order to expand the substrate scope of the already existing AmDHs. In addition, novel AmDHs will be generated starting from different wild-type amino acid dehydrogenases as scaffolds, whose amino acid and DNA sequences are available in databases, literature, libraries, etc. In particular, protein engineering will be focused on the specific chemical targets that are the objectives of the designed biocatalytic cascades and in addition, screening for more diverse substrates will also be carried out. Finally, the AmDHs will be used in combination with other enzymes such as alcohol dehydrogenases, oxidases, alkane monooxygenases, etc., to deliver variously functionalised amines and derivatives as final products with elevated yields, perfect chemo- regio- and stereoselectivity, enhanced atom efficiency and minimum environmental impact. Such an approach will be realised through the design of new pathways that will convert inexpensive starting materials from renewable resources, encompassing the internal recycling of redox equivalents, the use of inorganic ammonia as nitrogen source and, if necessary, only molecular oxygen as the innocuous additional oxidant. Water will be the sole by-product.

Max ERC Funding

1 497 270 €

Duration

Start date: 2015-05-01, End date: 2020-10-31

Project acronymBLOODCELLSCROSSTALK

ProjectThe Crosstalk Between Red And White Blood Cells: The Case Of Fish

Researcher (PI)Maria del Mar Ortega-Villaizan Romo

Host Institution (HI)UNIVERSIDAD MIGUEL HERNANDEZ DE ELCHE

Call DetailsStarting Grant (StG), LS9, ERC-2014-STG

SummaryFish are the phylogenetically oldest vertebrate group with an immune system with clear similarities to the immune system of mammals. However, it is an actual matter of fact that the current knowledge of the fish immune system seems to lack the key piece to complete the puzzle.
In 1953 Nelson described a new role of human red blood cells (RBCs) which would go beyond the simple transport of O2 to the tissues. This new role, involved in the defence against microbes, described the antibody and complement-dependent binding of microbial immune complexes to RBCs. Regardless of the importance of this finding in the field of microbial infection, this phenomenon has been poorly evaluated. Just recently, a set of biological processes relevant to immunity have been described in the RBCs of a diverse group of organisms, which include: pathogen recognition, pathogen binding and clearance and cytokines production. Furthermore, it has been demonstrated that nucleated erythrocytes from fish and avian species develop specific responses to different pathogen associated molecular patterns and produce soluble factors that modulate leukocyte activity.
In the light of these pieces of evidences, and in an attempt to improve the knowledge of the immune mechanism(s) responsible for fish protection against viral infections, we raised the question: could nucleated fish erythrocytes be the key mediators of the antiviral responses? To answer this question we decided to focus our project on the evaluation of the crosstalk between red and white blood cells in the scenario of fish viral infections and prophylaxis. For that a working model composed of the rainbow trout and the viral haemorrhagic septicaemia virus (VHSV) was chosen, being the objectives of the project to evaluate: i) the implication trout RBCs (tRBCs) in the clearance of VHSV, and ii) the involvement of tRBCs in the blood transportation of the glycoprotein G of VHSV (GVHSV), the antigen encoded by the DNA vaccine.

Fish are the phylogenetically oldest vertebrate group with an immune system with clear similarities to the immune system of mammals. However, it is an actual matter of fact that the current knowledge of the fish immune system seems to lack the key piece to complete the puzzle.
In 1953 Nelson described a new role of human red blood cells (RBCs) which would go beyond the simple transport of O2 to the tissues. This new role, involved in the defence against microbes, described the antibody and complement-dependent binding of microbial immune complexes to RBCs. Regardless of the importance of this finding in the field of microbial infection, this phenomenon has been poorly evaluated. Just recently, a set of biological processes relevant to immunity have been described in the RBCs of a diverse group of organisms, which include: pathogen recognition, pathogen binding and clearance and cytokines production. Furthermore, it has been demonstrated that nucleated erythrocytes from fish and avian species develop specific responses to different pathogen associated molecular patterns and produce soluble factors that modulate leukocyte activity.
In the light of these pieces of evidences, and in an attempt to improve the knowledge of the immune mechanism(s) responsible for fish protection against viral infections, we raised the question: could nucleated fish erythrocytes be the key mediators of the antiviral responses? To answer this question we decided to focus our project on the evaluation of the crosstalk between red and white blood cells in the scenario of fish viral infections and prophylaxis. For that a working model composed of the rainbow trout and the viral haemorrhagic septicaemia virus (VHSV) was chosen, being the objectives of the project to evaluate: i) the implication trout RBCs (tRBCs) in the clearance of VHSV, and ii) the involvement of tRBCs in the blood transportation of the glycoprotein G of VHSV (GVHSV), the antigen encoded by the DNA vaccine.

Max ERC Funding

1 823 250 €

Duration

Start date: 2015-04-01, End date: 2020-10-31

Project acronymBSMFLEET

ProjectChallenging the Standard Model using an extended Physics program in LHCb

Researcher (PI)Diego Martinez Santos

Host Institution (HI)UNIVERSIDAD DE SANTIAGO DE COMPOSTELA

Call DetailsStarting Grant (StG), PE2, ERC-2014-STG

SummaryWe know that the Standard Model (SM) of Particle Physics is not the ultimate theory of Nature. It misses a quantum description of gravity, it does not offer any explanation to the composition of Dark Matter, and the matter-antimatter unbalance of the Universe is predicted to be significantly smaller than what we actually see. Those are fundamental questions that still need an answer. Alternative models to SM exist, based on ideas such as SuperSymmetry or extra dimensions, and are currently being tested at the Large Hadron Collider (LHC) at CERN. But after the first run of the LHC the SM is yet unbeaten at accelerators, which imposes severe constraints in Physics beyond the SM (BSM). From this point, I see two further working directions: on one side, we must increase our precision in the previous measurements in order to access smaller BSM effects. On the other hand; we should attack the SM with a new fleet of observables sensitive to different BSM scenarios, and make sure that we are making full use of what the LHC offers to us. I propose to create a team at Universidade de Santiago de Compostela that will expand the use of LHCb beyond its original design, while also reinforcing the core LHCb analyses in which I played a leading role so far. LHCb has up to now collected world-leading samples of decays of b and c quarks. My proposal implies to use LHCb for collecting and analysing also world-leading samples of rare s quarks complementary to those of NA62. In the rare s decays the SM sources of Flavour Violation have a stronger suppression than anywhere else, and therefore those decays are excellent places to search for new Flavour Violating sources that otherwise would be hidden behind the SM contributions. It is very important to do this now, since we may not have a similar opportunity in years. In addition, the team will also exploit LHCb to search for μμ resonances predicted in models like NMSSM, and for which LHCb also offers a unique potential that must be used.

We know that the Standard Model (SM) of Particle Physics is not the ultimate theory of Nature. It misses a quantum description of gravity, it does not offer any explanation to the composition of Dark Matter, and the matter-antimatter unbalance of the Universe is predicted to be significantly smaller than what we actually see. Those are fundamental questions that still need an answer. Alternative models to SM exist, based on ideas such as SuperSymmetry or extra dimensions, and are currently being tested at the Large Hadron Collider (LHC) at CERN. But after the first run of the LHC the SM is yet unbeaten at accelerators, which imposes severe constraints in Physics beyond the SM (BSM). From this point, I see two further working directions: on one side, we must increase our precision in the previous measurements in order to access smaller BSM effects. On the other hand; we should attack the SM with a new fleet of observables sensitive to different BSM scenarios, and make sure that we are making full use of what the LHC offers to us. I propose to create a team at Universidade de Santiago de Compostela that will expand the use of LHCb beyond its original design, while also reinforcing the core LHCb analyses in which I played a leading role so far. LHCb has up to now collected world-leading samples of decays of b and c quarks. My proposal implies to use LHCb for collecting and analysing also world-leading samples of rare s quarks complementary to those of NA62. In the rare s decays the SM sources of Flavour Violation have a stronger suppression than anywhere else, and therefore those decays are excellent places to search for new Flavour Violating sources that otherwise would be hidden behind the SM contributions. It is very important to do this now, since we may not have a similar opportunity in years. In addition, the team will also exploit LHCb to search for μμ resonances predicted in models like NMSSM, and for which LHCb also offers a unique potential that must be used.

Max ERC Funding

1 499 855 €

Duration

Start date: 2015-04-01, End date: 2020-03-31

Project acronymCENNS

ProjectProbing new physics with Coherent Elastic Neutrino-Nucleus Scattering and a tabletop experiment

SummaryEver since the Higgs boson was discovered at the LHC in 2012, we had the confirmation that the Standard Model (SM) of particle physics has to be extended. In parallel, the long lasting Dark Matter (DM) problem, supported by a wealth of evidence ranging from precision cosmology to local astrophysical observations, has been suggesting that new particles should exist. Unfortunately, neither the LHC nor the DM dedicated experiments have significantly detected any exotic signals pointing toward a particular new physics extension of the SM so far.
With this proposal, I want to take a new path in the quest of new physics searches by providing the first high-precision measurement of the neutral current Coherent Elastic Neutrino-Nucleus Scattering (CENNS). By focusing on the sub-100 eV CENNS induced nuclear recoils, my goal is to reach unprecedented sensitivities to various exotic physics scenarios with major implications from cosmology to particle physics, beyond the reach of existing particle physics experiments. These include for instance the existence of sterile neutrinos and of new mediators, that could be related to the DM problem, and the possibility of Non Standard Interactions that would have tremendous implications on the global neutrino physics program.
To this end, I propose to build a kg-scale cryogenic tabletop neutrino experiment with outstanding sensitivity to low-energy nuclear recoils, called CryoCube, that will be deployed at an optimal nuclear reactor site. The key feature of this proposed detector technology is to combine two target materials: Ge-semiconductor and Zn-superconducting metal. I want to push these two detector techniques beyond the state-of-the-art performance to reach sub-100 eV energy thresholds with unparalleled background rejection capabilities.
As my proposed CryoCube detector will reach a 5-sigma level CENNS detection significance in a single day, it will be uniquely positioned to probe new physics extensions beyond the SM.

Ever since the Higgs boson was discovered at the LHC in 2012, we had the confirmation that the Standard Model (SM) of particle physics has to be extended. In parallel, the long lasting Dark Matter (DM) problem, supported by a wealth of evidence ranging from precision cosmology to local astrophysical observations, has been suggesting that new particles should exist. Unfortunately, neither the LHC nor the DM dedicated experiments have significantly detected any exotic signals pointing toward a particular new physics extension of the SM so far.
With this proposal, I want to take a new path in the quest of new physics searches by providing the first high-precision measurement of the neutral current Coherent Elastic Neutrino-Nucleus Scattering (CENNS). By focusing on the sub-100 eV CENNS induced nuclear recoils, my goal is to reach unprecedented sensitivities to various exotic physics scenarios with major implications from cosmology to particle physics, beyond the reach of existing particle physics experiments. These include for instance the existence of sterile neutrinos and of new mediators, that could be related to the DM problem, and the possibility of Non Standard Interactions that would have tremendous implications on the global neutrino physics program.
To this end, I propose to build a kg-scale cryogenic tabletop neutrino experiment with outstanding sensitivity to low-energy nuclear recoils, called CryoCube, that will be deployed at an optimal nuclear reactor site. The key feature of this proposed detector technology is to combine two target materials: Ge-semiconductor and Zn-superconducting metal. I want to push these two detector techniques beyond the state-of-the-art performance to reach sub-100 eV energy thresholds with unparalleled background rejection capabilities.
As my proposed CryoCube detector will reach a 5-sigma level CENNS detection significance in a single day, it will be uniquely positioned to probe new physics extensions beyond the SM.

Max ERC Funding

1 495 000 €

Duration

Start date: 2019-02-01, End date: 2024-01-31

Project acronymcollectiveQCD

ProjectCollectivity in small, srongly interacting systems

Researcher (PI)Korinna ZAPP

Host Institution (HI)LUNDS UNIVERSITET

Call DetailsStarting Grant (StG), PE2, ERC-2018-STG

SummaryIn collisions of heavy nuclei at collider energies, for instance at the Large Hadron Collider (LHC) at CERN, the energy density is so high that an equilibrated Quark-Gluon Plasma (QGP), an exotic state of matter consisting of deconfined quarks and gluons, is formed. In proton-proton (p+p) collisions, on the other hand, the density of produced particles is low. The traditional view on such reactions is that final state particles are free and do not rescatter. This picture is challenged by recent LHC data, which found features in p+p collisions that are indicative of collective behaviour and/or the formation of a hot and dense system. These findings have been taken as signs of QGP formation in p+p reactions. Such an interpretation is complicated by the fact that jets, which are the manifestation of very energetic quarks and gluons, are quenched in heavy ion collisions, but appear to be unmodified in p+p reactions. This is puzzling because collectivity and jet quenching are caused by the same processes. So far there is no consensus about the interpretation of these results, which is also due to a lack of suitable tools.
It is the objective of this proposal to address the question whether there are collective effects in p+p collisions. To this end two models capable of describing all relevant aspects of p+p and heavy ion collisions will be developed. They will be obtained by extending a successful description of p+p to heavy ion reactions and vice versa.
The answer to these questions will either clarify the long-standing problem how collectivity emerges from fundamental interactions, or it will necessitate qualitative changes to our interpretation of collective phenomena in p+p and/or heavy ion collisions.
The PI is in a unique position to accomplish this goal, as she has spent her entire career working on different aspects of p+p and heavy ion collisions. The group in Lund is the ideal host, as it is very active in developing alternative interpretations of the data.

In collisions of heavy nuclei at collider energies, for instance at the Large Hadron Collider (LHC) at CERN, the energy density is so high that an equilibrated Quark-Gluon Plasma (QGP), an exotic state of matter consisting of deconfined quarks and gluons, is formed. In proton-proton (p+p) collisions, on the other hand, the density of produced particles is low. The traditional view on such reactions is that final state particles are free and do not rescatter. This picture is challenged by recent LHC data, which found features in p+p collisions that are indicative of collective behaviour and/or the formation of a hot and dense system. These findings have been taken as signs of QGP formation in p+p reactions. Such an interpretation is complicated by the fact that jets, which are the manifestation of very energetic quarks and gluons, are quenched in heavy ion collisions, but appear to be unmodified in p+p reactions. This is puzzling because collectivity and jet quenching are caused by the same processes. So far there is no consensus about the interpretation of these results, which is also due to a lack of suitable tools.
It is the objective of this proposal to address the question whether there are collective effects in p+p collisions. To this end two models capable of describing all relevant aspects of p+p and heavy ion collisions will be developed. They will be obtained by extending a successful description of p+p to heavy ion reactions and vice versa.
The answer to these questions will either clarify the long-standing problem how collectivity emerges from fundamental interactions, or it will necessitate qualitative changes to our interpretation of collective phenomena in p+p and/or heavy ion collisions.
The PI is in a unique position to accomplish this goal, as she has spent her entire career working on different aspects of p+p and heavy ion collisions. The group in Lund is the ideal host, as it is very active in developing alternative interpretations of the data.

Max ERC Funding

1 500 000 €

Duration

Start date: 2019-02-01, End date: 2024-01-31

Project acronymCONSTRAINTS

ProjectEcophysiological and biophysical constraints on domestication in crop plants

SummaryA fundamental question in biology is how constraints drive phenotypic changes and the diversification of life. We know little about the role of these constraints on crop domestication, nor how artificial selection can escape them. CONSTRAINTS questions whether crop domestication has shifted ecophysiological and biophysical traits related to resource acquisition, use and partitioning, and how trade-offs between them have constrained domestication and can limit future improvements in both optimal and sub-optimal conditions.
The project is based on three objectives: 1. revealing the existence (or lack) of generic resource-use domestication syndrome in crop science; 2. elucidating ecophysiological and biophysical trade-offs within crop science and delineating the envelope of constraints for artificial selection; 3. examining the shape of ecophysiological and biophysical trade-offs in crop species when grown in sub-optimal environmental conditions. This project will be investigated within and across crop species thanks to a core panel of 12 studied species (maize, sunflower, Japanese rice, sorghum, durum wheat, bread wheat, alfalfa, orchardgrass, silvergrass, pea, colza, vine) for which data and collections (ca. 1,300 genotypes total) are already available to the PI, and additional high throughput phenotyping using automatons. Additional species will be used for specific tasks: (i) a panel of 30 species for a comparative analysis of crop species and their wild progenitors; (ii) 400 worldwide accessions of Arabidopsis thaliana for a genome-wide association study of resource-use traits. Collectively, we will use a multiple-tool approach by using: field measurement, high-throughput phenotyping, common-garden experiment, comparative analysis using databases, modelling, genomics.
The ground-breaking nature of the project holds in the nature of the questions asked and in the unique opportunity to transfer knowledge from ecology and evolutionary biology to crop species.

A fundamental question in biology is how constraints drive phenotypic changes and the diversification of life. We know little about the role of these constraints on crop domestication, nor how artificial selection can escape them. CONSTRAINTS questions whether crop domestication has shifted ecophysiological and biophysical traits related to resource acquisition, use and partitioning, and how trade-offs between them have constrained domestication and can limit future improvements in both optimal and sub-optimal conditions.
The project is based on three objectives: 1. revealing the existence (or lack) of generic resource-use domestication syndrome in crop science; 2. elucidating ecophysiological and biophysical trade-offs within crop science and delineating the envelope of constraints for artificial selection; 3. examining the shape of ecophysiological and biophysical trade-offs in crop species when grown in sub-optimal environmental conditions. This project will be investigated within and across crop species thanks to a core panel of 12 studied species (maize, sunflower, Japanese rice, sorghum, durum wheat, bread wheat, alfalfa, orchardgrass, silvergrass, pea, colza, vine) for which data and collections (ca. 1,300 genotypes total) are already available to the PI, and additional high throughput phenotyping using automatons. Additional species will be used for specific tasks: (i) a panel of 30 species for a comparative analysis of crop species and their wild progenitors; (ii) 400 worldwide accessions of Arabidopsis thaliana for a genome-wide association study of resource-use traits. Collectively, we will use a multiple-tool approach by using: field measurement, high-throughput phenotyping, common-garden experiment, comparative analysis using databases, modelling, genomics.
The ground-breaking nature of the project holds in the nature of the questions asked and in the unique opportunity to transfer knowledge from ecology and evolutionary biology to crop species.

Max ERC Funding

1 499 979 €

Duration

Start date: 2015-06-01, End date: 2021-05-31

Project acronymCurvedSusy

ProjectDynamics of Supersymmetry in Curved Space

Researcher (PI)Guido Festuccia

Host Institution (HI)UPPSALA UNIVERSITET

Call DetailsStarting Grant (StG), PE2, ERC-2014-STG

SummaryQuantum field theory provides a theoretical framework to explain quantitatively natural phenomena as diverse as the fluctuations in the cosmic microwave background, superconductivity, and elementary particle interactions in colliders. Even if we use quantum field theories in different settings, their structure and dynamics are still largely mysterious. Weakly coupled systems can be studied perturbatively, however many natural phenomena are characterized by strong self-interactions (e.g. high T superconductors, nuclear forces) and their analysis requires going beyond perturbation theory. Supersymmetric field theories are very interesting in this respect because they can be studied exactly even at strong coupling and their dynamics displays phenomena like confinement or the breaking of chiral symmetries that occur in nature and are very difficult to study analytically.
Recently it was realized that many interesting insights on the dynamics of supersymmetric field theories can be obtained by placing these theories in curved space preserving supersymmetry. These advances have opened new research avenues but also left many important questions unanswered. The aim of our research programme will be to clarify the dynamics of supersymmetric field theories in curved space and use this knowledge to establish new exact results for strongly coupled supersymmetric gauge theories. The novelty of our approach resides in the systematic use of the interplay between the physical properties of a supersymmetric theory and the geometrical properties of the space-time it lives in. The analytical results we will obtain, while derived for very symmetric theories, can be used as a guide in understanding the dynamics of many physical systems. Besides providing new tools to address the dynamics of quantum field theory at strong coupling this line of investigation could lead to new connections between Physics and Mathematics.

Quantum field theory provides a theoretical framework to explain quantitatively natural phenomena as diverse as the fluctuations in the cosmic microwave background, superconductivity, and elementary particle interactions in colliders. Even if we use quantum field theories in different settings, their structure and dynamics are still largely mysterious. Weakly coupled systems can be studied perturbatively, however many natural phenomena are characterized by strong self-interactions (e.g. high T superconductors, nuclear forces) and their analysis requires going beyond perturbation theory. Supersymmetric field theories are very interesting in this respect because they can be studied exactly even at strong coupling and their dynamics displays phenomena like confinement or the breaking of chiral symmetries that occur in nature and are very difficult to study analytically.
Recently it was realized that many interesting insights on the dynamics of supersymmetric field theories can be obtained by placing these theories in curved space preserving supersymmetry. These advances have opened new research avenues but also left many important questions unanswered. The aim of our research programme will be to clarify the dynamics of supersymmetric field theories in curved space and use this knowledge to establish new exact results for strongly coupled supersymmetric gauge theories. The novelty of our approach resides in the systematic use of the interplay between the physical properties of a supersymmetric theory and the geometrical properties of the space-time it lives in. The analytical results we will obtain, while derived for very symmetric theories, can be used as a guide in understanding the dynamics of many physical systems. Besides providing new tools to address the dynamics of quantum field theory at strong coupling this line of investigation could lead to new connections between Physics and Mathematics.

Max ERC Funding

1 145 879 €

Duration

Start date: 2015-09-01, End date: 2020-08-31

Project acronymCUSTOM-SENSE

ProjectCustom-made biosensors – Accelerating the transition to a bio-based economy

Researcher (PI)Jan Marienhagen

Host Institution (HI)FORSCHUNGSZENTRUM JULICH GMBH

Call DetailsStarting Grant (StG), LS9, ERC-2014-STG

SummaryHow will we meet the globally growing demand for pharmaceutically active compounds, nutrients and fine chemicals when crude oil resources are dwindling? For decades, biotechnologists have been engineering microorganisms to produce valuable compounds from sugar and biomass. However, a lack of knowledge regarding the host cell metabolism as well as long and laborious development times render this approach challenging to this day.
I want to establish a platform to engineer transcriptional biosensors for the intracellular detection of heterologous compounds in single cells. The application of these sensors in combination with flow cytometry and next-generation sequencing will enable high-throughput engineering of microorganisms at the single-cell level with unprecedented speed and simplicity.
In the field of biotechnology, this new technology will be a powerful tool for the (i) accelerated directed evolution of genes and pathways in vivo, (ii) functional integration of heterologous genes or whole synthetic pathways into the metabolism of microorganisms for the production of small valuable metabolites, (iii) genome engineering of industrially relevant microorganisms and (iv) adaptation of production strains to process conditions.
Furthermore, during CUSTOM-SENSE, biosensors will also prove to be a valuable tool to answer questions in basic science because they will help to elucidate the function of unknown genes and aid the discovery of novel and unexpected functional links in cellular metabolism.
I am in an exclusive position to pursue this goal of developing an engineering platform for custom-made biosensors due to the previous invention of biosensors at IBG-1. The starting grant would allow me to compete with Patrick D. Cirino (University of Houston, USA), who is working on a similar approach, and Christina D. Smolke (Stanford University/Caltech, USA), who is focusing on RNA devices for metabolite detection.

How will we meet the globally growing demand for pharmaceutically active compounds, nutrients and fine chemicals when crude oil resources are dwindling? For decades, biotechnologists have been engineering microorganisms to produce valuable compounds from sugar and biomass. However, a lack of knowledge regarding the host cell metabolism as well as long and laborious development times render this approach challenging to this day.
I want to establish a platform to engineer transcriptional biosensors for the intracellular detection of heterologous compounds in single cells. The application of these sensors in combination with flow cytometry and next-generation sequencing will enable high-throughput engineering of microorganisms at the single-cell level with unprecedented speed and simplicity.
In the field of biotechnology, this new technology will be a powerful tool for the (i) accelerated directed evolution of genes and pathways in vivo, (ii) functional integration of heterologous genes or whole synthetic pathways into the metabolism of microorganisms for the production of small valuable metabolites, (iii) genome engineering of industrially relevant microorganisms and (iv) adaptation of production strains to process conditions.
Furthermore, during CUSTOM-SENSE, biosensors will also prove to be a valuable tool to answer questions in basic science because they will help to elucidate the function of unknown genes and aid the discovery of novel and unexpected functional links in cellular metabolism.
I am in an exclusive position to pursue this goal of developing an engineering platform for custom-made biosensors due to the previous invention of biosensors at IBG-1. The starting grant would allow me to compete with Patrick D. Cirino (University of Houston, USA), who is working on a similar approach, and Christina D. Smolke (Stanford University/Caltech, USA), who is focusing on RNA devices for metabolite detection.

Max ERC Funding

1 482 220 €

Duration

Start date: 2015-05-01, End date: 2021-04-30

Project acronymDARKJETS

ProjectDiscovery strategies for Dark Matter and new phenomena in hadronic signatures with the ATLAS detector at the Large Hadron Collider

Researcher (PI)Caterina Doglioni

Host Institution (HI)LUNDS UNIVERSITET

Call DetailsStarting Grant (StG), PE2, ERC-2015-STG

SummaryThe Standard Model of Particle Physics describes the fundamental components of ordinary matter and their interactions. Despite its success in predicting many experimental results, the Standard Model fails to account for a number of interesting phenomena. One phenomenon of particular interest is the large excess of unobservable (Dark) matter in the Universe. This excess cannot be explained by Standard Model particles. A compelling hypothesis is that Dark Matter is comprised of particles that can be produced in the proton-proton collisions from the Large Hadron Collider (LHC) at CERN.
Within this project, I will build a team of researchers at Lund University dedicated to searches for signals of the presence of Dark Matter particles. The discovery strategies employed seek the decays of particles that either mediate the interactions between Dark and Standard Model particles or are produced in association with Dark Matter. These new particles manifest in detectors as two, three, or four collimated jets of particles (hadronic jets).
The LHC will resume delivery of proton-proton collisions to the ATLAS detector in 2015. Searches for new, rare, low mass particles such as Dark Matter mediators have so far been hindered by constraints on the rates of data that can be stored. These constraints will be overcome through the implementation of a novel real-time data analysis technique and a new search signature, both introduced to ATLAS by this project. The coincidence of this project with the upcoming LHC runs and the software and hardware improvements within the ATLAS detector is a unique opportunity to increase the sensitivity to hadronically decaying new particles by a large margin with respect to any previous searches. The results of these searches will be interpreted within a comprehensive and coherent set of theoretical benchmarks, highlighting the strengths of collider experiments in the global quest for Dark Matter.

The Standard Model of Particle Physics describes the fundamental components of ordinary matter and their interactions. Despite its success in predicting many experimental results, the Standard Model fails to account for a number of interesting phenomena. One phenomenon of particular interest is the large excess of unobservable (Dark) matter in the Universe. This excess cannot be explained by Standard Model particles. A compelling hypothesis is that Dark Matter is comprised of particles that can be produced in the proton-proton collisions from the Large Hadron Collider (LHC) at CERN.
Within this project, I will build a team of researchers at Lund University dedicated to searches for signals of the presence of Dark Matter particles. The discovery strategies employed seek the decays of particles that either mediate the interactions between Dark and Standard Model particles or are produced in association with Dark Matter. These new particles manifest in detectors as two, three, or four collimated jets of particles (hadronic jets).
The LHC will resume delivery of proton-proton collisions to the ATLAS detector in 2015. Searches for new, rare, low mass particles such as Dark Matter mediators have so far been hindered by constraints on the rates of data that can be stored. These constraints will be overcome through the implementation of a novel real-time data analysis technique and a new search signature, both introduced to ATLAS by this project. The coincidence of this project with the upcoming LHC runs and the software and hardware improvements within the ATLAS detector is a unique opportunity to increase the sensitivity to hadronically decaying new particles by a large margin with respect to any previous searches. The results of these searches will be interpreted within a comprehensive and coherent set of theoretical benchmarks, highlighting the strengths of collider experiments in the global quest for Dark Matter.

SummaryYellow rust (YR) disease is a major threat to cereal crops and grasses worldwide, causing significant losses to the global wheat harvest each year. The long-term aim of this research is to develop new varieties of wheat with enhanced resistance to YR. To do this, it is essential to understand host specificity - the ability of the pathogen to specialize on particular grass hosts, coupled with the ability of the host to resist infection by different strains of YR.
I recently pioneered a field-based 'pathogenomics' approach to enable a comprehensive evaluation of the genetic diversity of YR. This new method provides unparalleled resolution of the pathogen population that can identify gene families associated with the ability to cause disease on all the major hosts of YR in Europe, namely wheat barley, rye, triticale and cocksfoot grass. Using this approach, I previously uncovered a genetically distinct population of YR on triticale and showed that these isolates contained gene clusters that were specifically expressed in all isolates identified on triticale and had no or negligible levels of expression in all wheat YR isolates.
In this ERC project, I will use the pathogenomics approach to collect an extensive dataset of YR on all its major hosts, aiming to characterise genomic regions and the genes they encode to understand the underlying regulatory mechanisms that drive host specialization and adaptation. I will then assess changes at the transcriptomic level in closely related host-specialized YR races to provide insights into how pathogens adapt to new hosts. In parallel, I will identify host targets of effectors from YR to resolve the underlying molecular processes that are targeted by the pathogen to enable successful host-specific colonization. I will then disrupt the function of these host targets using precision genome editing to determine their contribution to YR pathogenicity and reveal novel susceptibility genes that are essential for pathogen progression.

Yellow rust (YR) disease is a major threat to cereal crops and grasses worldwide, causing significant losses to the global wheat harvest each year. The long-term aim of this research is to develop new varieties of wheat with enhanced resistance to YR. To do this, it is essential to understand host specificity - the ability of the pathogen to specialize on particular grass hosts, coupled with the ability of the host to resist infection by different strains of YR.
I recently pioneered a field-based 'pathogenomics' approach to enable a comprehensive evaluation of the genetic diversity of YR. This new method provides unparalleled resolution of the pathogen population that can identify gene families associated with the ability to cause disease on all the major hosts of YR in Europe, namely wheat barley, rye, triticale and cocksfoot grass. Using this approach, I previously uncovered a genetically distinct population of YR on triticale and showed that these isolates contained gene clusters that were specifically expressed in all isolates identified on triticale and had no or negligible levels of expression in all wheat YR isolates.
In this ERC project, I will use the pathogenomics approach to collect an extensive dataset of YR on all its major hosts, aiming to characterise genomic regions and the genes they encode to understand the underlying regulatory mechanisms that drive host specialization and adaptation. I will then assess changes at the transcriptomic level in closely related host-specialized YR races to provide insights into how pathogens adapt to new hosts. In parallel, I will identify host targets of effectors from YR to resolve the underlying molecular processes that are targeted by the pathogen to enable successful host-specific colonization. I will then disrupt the function of these host targets using precision genome editing to determine their contribution to YR pathogenicity and reveal novel susceptibility genes that are essential for pathogen progression.